查看文章

Acquired resistance (AR) to selective FLT3 inhibitors, is a significant clinical problem in the treatment of FLT3mt AML. AR can emerge through metabolic reprogramming, a process dependent on Aurora kinase B, or through secondary FLT3 TKD mt. EP0042 was developed as an orally bioavailable potent inhibitor of FLT3 and Aurora kinases, as a potential strategy to address the issue of FLT3 inhibitor resistance. EP0042 selectively inhibits the FLT3/Aurora pathways at similar nanomolar concentrations. Dual inhibition of FLT3/Aurora kinase has been shown to overcome AR to selective FLT3 inhibition both in vitro and in vivo (Moore A et al. Leukemia 2012; 26: 1462-70; Tariq M et al. Br J Cancer 2021; 125: 966-74). EP0042 has resulted in inhibition of tumor growth in FLT3-ITD and FLT3-ITD-TKD human tumor xenograft models and in quizartinib-resistant primary AML samples (Moore A et al. Blood Advances 2020; 4 …